Design, Synthesis, and Testing of a Molecular Truck for Colonic Delivery of 5-Aminosalicylic Acid

A molecular scaffold bearing eight terminal alkyne groups was synthesized from sucrose. Eight copies of an azide-terminated, azo-linked precursor to 5-aminosalicylic acid were attached to the scaffold via copper(I)-catalyzed azide–alkyne cycloaddition. The resulting compound was evaluated in a DSS model of colitis in BALB/c mice against sulfasalazine as a control. Two independent studies verified that the novel pro-drug, administered in a dose calculated to result in an equimolar 5-ASA yield, outperformed sulfasalazine in terms of protection from mucosal inflammation and T cell activation. A separate study established that 5-ASA appeared in feces produced 24–48 h following administration of the pro-drug. Thus, a new, orally administered pro-drug form of 5-aminosalicylic acid has been developed and successfully demonstrated

Revisit: The Synthesis of 3-amino pyrazoles promoted by p-toluenesulfonic acid as an efficient catalyst under solvent and solvent-free conditions

An efficient and facile synthesis of 3-amino pyrazoles has been described. The reaction of b-keto nitriles with hydrazines using p-toluenesulfonic acid as an efficient catalyst under solvent and solvent-free conditions afford corresponding 3-amino pyrazoles in excellent yields&#x0D; Introduction&#x0D;  Pyrazoles, in particular 3-amino pyrazoles are an important class of compounds in medicinal chemistry and it has been well documented to posses antihypertensive,1 antibacterial,2 anti-inflammatory muscle relaxant3,4 and inhibitors of cyclin dependent kinases (CDK) such as CDK2/cycling A-E.5 They are also potent and selective Aurora kinase inhibitors.6,7 In addition the 3-amino pyrazoles also have industrial appliance in inhibition of corrosion on metals such as Zn, Cu, Al and Brass.8&#x0D; Despite their importance from a pharmacological, industrial and synthetic point of view, comparatively few methods for the preparation of 3-amino pyrazoles have been reported. These includes condensation of hydrazines with β-keto nitriles,9 β-formyl nitriles,4 β-methoxy vinyl nitriles,10 α-nitrilo ethyl acetate11 and solid phase synthesis of 5-substituted amino pyrazoles.12  Unfortunately many of these processes suffer from one or other limitations such as incompletion of starting materials, long reaction times, with unsatisfactory yields. Thus there is a need for the development of an alternate route to construct the 3-amino pyrazoles.&#x0D; In recent years, p-toluenesulfonic acid is used as an efficient catalyst in various organic transformations,13 also it should be noted that p-toluenesulfonic acid is cheap, commercially available and comparatively non-toxic. The organic reactions assisted by microwaves,14 in particular have been gained special attention. One reason is that the use of microwave activation in organic synthesis can increase the purity of the resulting products, enhance the chemical yield and shorten the reaction times. And also organic reactions carried out in the absence of solvent, has been attracting attention of chemists due to ease of processing to the further step and eco-friendly in nature. In the case of synthesis of 3-amino pyrazoles, we thought that there is a scope for further innovation towards short reaction times and better yields. Here, we report an efficient and facile method for the synthesis of 3-amino pyrazoles catalyzed by p-toluenesulfonic acid under solvent and solvent-free conditions.&#x0D; Scheme 1&#x0D; Results &amp; discussion &#x0D; Reaction of benzoyl acetonitrile i. e. b-keto nitrile15 with 4-hydrazinobenzoic acid under reflux conditions in absolute ethanol for 8-10hr resulted in the formation of the corresponding 3-amino pyrazoles in &lt;90% yield. However, we carried out the reaction in presence of catalytic amounts of p-toluenesulfonic acid (0.01 equiv.) and found reaction is completed in 45 min with nearly 100% conversion (Table 1, entry 7). This success has encouraged us to extend the generality of the reaction; various hydrazines with various b-keto nitriles in presence p-toluenesulfonic acid proceeded efficiently and smoothly at refluxing temperature and the products are obtained in excellent yields. And the reaction conditions are very favorable, no by-products are observed (Table 1, Method A).&#x0D; We further investigated the reaction conditions to improve the reaction conditions. It has been found that, b-keto nitrile 1 (1 mmol) and hydrazine 2 (1 mmol) reacts very rapidly (&lt;5min) to give 3-amino pyrazoles in the presence of p-toluenesulfonic acid under microwave irradiation in solvent-free conditions (Table 1, Method B). The experimental procedure for this reaction is remarkably simple and no solvents or inert atmosphere is required. Under above conditions, in many cases it is noticed that in the absence of p-toluenesulfonic acid, the reaction is incomplete and uncyclized product was isolated along with pyrazole.&#x0D; &#x0D; Table 2: Synthesis of 3-Amino pyrazole catalyzed by p-toluenesulfonic acid under solvent and solvent free conditions. &#x0D; a Isolated yields after crystallization/column chromatography and all products gave satisfactory spectral (IR, 1HNMR and MASS) and analytical data&#x0D;  &#x0D; In summary, the present procedures for the synthesis of 3-amino pyrazole have been developed by condensation reaction of hydrazines with b-keto nitriles catalyzed by p-toluenesulfonic acid under solvent and solvent free conditions. The advantage of present method is high efficient, reduced reaction time and inexpensive catalyst with high yields of products and simple experimental work-up procedure, which makes it, is a useful and important addition to the present existing methodologies.&#x0D; Acknowledgements: The authors are thankful to Director IICT for his constant encouragement and DOD New Delhi for providing fellowship.&#x0D; Typical Experimental procedure (Method A, Conventional): A mixture of b-keto nitile (10 mmol), hydrazine (10 mmol) and to this p-TSA (0.1mmol) was added and refluxed in absolute ethanol for appropriate time (Table 1, Method A). After completion of the reaction, as monitored by TLC, the solvent was evaporated under reduced pressure. The product was extracted into ethyl acetate (3 x 20 mL). The combined organic layer was washed with saturated sodium bicarbonate followed by brine solution, then dried over anhydrous sodium sulphate. The solvent was removed to afford crude product and purified by column chromatography.&#x0D; Typical Experimental procedure (Method B, Microwave): A mixture of b-keto nitile (10 mmol), hydrazine (10 mmol), p-TSA (0.1mmol) was suspended in water (1mL) in a reaction vessel, sealed without degassing and was subjected to microwave irradiation at 450Watt. at 1350C for appropriate time (Table 1, Method B). After completion of the reaction, as monitored by TLC, the reaction mass was cooled and product was extracted into ethyl acetate (3 x 20 mL). The combined organic layer was washed with saturated sodium bicarbonate followed by brine solution, then dried over anhydrous sodium sulphate. The solvent was removed under reduced pressure to afford crude product, it was purified by recrystallized from ethanol/column chromatography to give corresponding pure 3-amino pyrazoles.&#x0D; 3a: IR (KBr): 3418, 1618, 1509, 1009, 762, 707 cm-1; 1H NMR (200 MHz, DMSO+CDCl3): δ 1.25 (s, 9H), 5.85 (s, 1H); EIMS: m/z 139; Anal. Calcd. for C7H13N3: C, 60.431; H, 9.352; N, 30.215. Found: C, 60.399; H, 9.412, N, 30.186.&#x0D; 3b: IR (KBr): 3420, 1620, 1520, 750 cm-1; 1H NMR (200 MHz, DMSO+CDCl3): δ 2.26 (s, 3H), 4.75 (s, 2H br), 7.40 (s, 5H); EIMS:  m/z 173; Anal. Calcd. for C10H11N3: C, 69.280; H, 6.350; N, 24.277. Found: C, 69.340; H, 6.401, N, 24.258.&#x0D; 3c: IR (KBr): 3415, 1618, 1124, 613 cm-1; 1H NMR (200 MHz, DMSO+CDCl3) δ 4.25 (s, 2H br.), 5.75 (s, 1H), 7.30 (m, 5H); EIMS: m/z 157; Anal. Calcd. for C9H9N3: C, 67.924; H, 5.660; N, 26.415. Found: C, 67.905; H, 5.698, N, 26.396.&#x0D; 3d: IR (neat): 3448, 1636 cm-1; 1H NMR (200 MHz, DMSO+CDCl3): δ 5.5 (s, 1H), 7.25 (d, 2H, J = 8.25Hz), 7.35 (d, 2H, J = 8.25Hz); EIMS: m/z 193, 195; Anal. Calcd. for C9H8ClN3: C, 55.958; H, 4.145; Cl, 18.393; N, 21.761. Found: C, 55.826; H, 4.164; Cl, 18.308; N, 21.700.&#x0D; 3e: IR (KBr): 3413, 1618, 1511, 1108, 613 cm-1; 1H NMR (200 MHz, DMSO+CDCl3): δ 2.50 (s, 3H), 5.95 (s, 1H), 7.45 (d, 2H, J = 8.20Hz), 7.75 (d, 2H, J = 8.20Hz); EIMS: m/z 173. Anal. Calcd. for C10H11N3: C, 69.364; H, 6.358; N, 24.277. Found: C, 69.340; H, 6.401; N, 24.258.&#x0D; 3f: IR (KBr): 3415, 1694, 1615, 1179, 616 cm-1; 1H NMR (200 MHz, DMSO+CDCl3): δ 5.68 (s, 1H), 6.41 (s, 1H), 6.59 (s, 1H), 7.4 (s, 1H); EIMS: m/z 149; Anal. Calcd. for C7H7N3O: C, 56.375; H, 4.697; N, 28.187; O, 10.738. Found: C, 56.369; H, 4.730; N, 28.173; O, 10.736.&#x0D; 3g: IR (KBr): 3414, 1616, 1091 cm-1; 1H NMR (200 MHz, DMSO+CDCl3): δ 6.60 (s, 1H), 7.40 (m, 5H), 7.8 (d, 2H, J = 8.50Hz), 8.40 (d, 2H, J = 8.50Hz); EIMS: m/z 279; Anal. Calcd. for C16H13N3O2: C, 68.817; H, 4.659; N, 15.053; O, 11,469. Found: C, 68.806; H, 4.691; N, 15.044; O, 11.456.&#x0D; 3h: IR (KBr): 3414, 1617, 1383, 618 cm-1; 1H NMR (200 MHz, DMSI+CDCl3): δ 5.9 (s, 1H), 7.15 (m, 5H), 7.35 (d, 1H, J = 8.15Hz), 7.60 (t, 1H, J = 3.15Hz), 7.85 (d, 1H, J = 8.25Hz), 7.9 (d, 1H, J = 8.15Hz), 8.30 (s, 1H); EIMS: m/z 279; Anal. Calcd. for C16H13N3O2: C, 68.817; H, 4.659; N, 15.053; O, 11.469. Found: C, 68.806; H, 4.691; N, 15.044; O, 11.456.&#x0D; 3i: IR (KBr): 3415, 1618, 1285, 761 cm-1; 1H NMR (200 MHz, DMSO+CDCl3): δ 1.25 (t, 3H), 3.90 (q, 2H), 6.25 (s, 1H), 7.40 (m, 5H), 7.7 (d, 2H, J = 8.25Hz), 8.05 (d, 2H, J = 8.25Hz); EIMS: m/z 313;&#x0D; 3j: IR (KBr): 3415, 1657, 1615, 1384, 1121, 758 cm-1; 1H NMR (200 MHz, DMSO+CDCl3): δ 1.25 (t, 3H), 4.25 (q, 2H), 4.925 (s, 2H), 5.85 (s, 1H), 7.5 (m, 5H); EIMS: m/z 245; Anal. Calcd. for C13H15N3O2: C, 63.673; H, 6.122; N, 17.142; O, 13.067. Found: C, 63.658; H, 6.164; N, 17.131; O, 13.045.&#x0D; 3k: IR (KBr): 3416, 1650, 1384, 1120, 758 cm-1; 1H NMR (200 MHz, DMSO+CDCl3) δ 6.02 (s, 1H), 7.15 (d, 2H, J = 8.15Hz), 7.35 (d, 2H, J = 8.23Hz), 7.60 (d, 2H, J = 8.15Hz), 8.10 (d, 2H, J = 8.23Hz); EIMS: m/z 303, 305; Anal. Calcd. for C16H12ClN3O2: C, 61.341; H, 3.833; Cl, 11.341; N, 13.415; O, 10.223. Found: C, 61.252; H, 3.855; Cl, 11.299; N, 13.393; O, 10.198.&#x0D; 3l: IR (KBr): 3415, 1650, 1090 cm-1; 1H NMR (200 MHz, DMSO+CDCl3) δ 6.8 (s, 1H), 7.4 (d, 2H, J = 8.15Hz), 7.6 (t, 1H, J = 3.00Hz), 7.8 (d, 3H, J = 8.25Hz), 8.1 (d, 1H, J = 8.25Hz), 8.3 (s, 1H, J = 8.15Hz), 9.93 (s, 1H); EIMS: m/z 303, 305; Anal. Calcd. for C16H12ClN3O2: C, 61.341; H, 3.833; Cl, 11.341; N, 13.415; O, 10.223. Found: C, 61.252; H, 3.855; Cl, 11.299; N, 13.393; O, 10.198.&#x0D; 3m: IR (KBr): 3415, 1617, 1384, 764, 619 cm-1; 1H NMR (200MHz, DMSO+CDCl3) δ 2.37 (s, 3H), 3.75 (s, 2H broad), 7.1 (d, 2H, J = 8.22Hz), 7.4 (d, 2H, J = 8.15Hz), 7.7 (d, 2H, J = 8.15Hz), 8.0 (d, 2H, J = 8.22Hz); EIMS: m/z 291; Anal. Calcd. for C17H15N3O2: C, 69.624; H, 5.119; N, 14.334; O, 10.921. Found: C, 69.611; H, 5.154; N, 14.325; O, 10.908.           &#x0D; 3n: IR (KBr): 3415, 1618, 1384, 1216, 1047, 816, 619, 476 cm-1; 1H NMR (200 MHz, DMSO+CDCl3) δ 1.25 (t, 3H), 2.50 (s, 3H), 3.90 (q, 2H), 6.25 (s, 1H), 7.1 (d, 2H, J = 8.25Hz), 7.6 (d, 2H, J = 8.25Hz), 7.7 (d, 2H, J = 8.15Hz), 8.1 (d, 2H, J = 8.15Hz); EIMS: m/z 328; Anal. Calcd. for C17H17N3O2­­­­­­­­S: C, 62.385; H, 5.198; N, 12.84; O, 9.785; S, 9.785. Found: C, 62.365; H, 5.233; N, 12.834; O, 9.773; S, 9.793.&#x0D; 3o: 1H NMR (200 MHz, DMSO+CDCl3): δ 1.26 (s, 9H), 5.95 (s, 1H), 7.60 (d, 2H, J = 8.80Hz), 8.50 (d, 2H, J = 8.80Hz); EIMS: m/z 260.&#x0D; 3p: 1H NMR (200 MHz, DMSO+CDCl3): δ 2.26 (s, 3H), 7.40 (s, 5H), 7.62 (d, 2H, J = 8.60Hz), 8.56 (d, 2H, J = 8.60Hz); EIMS:  m/z 294.&#x0D; 3q: 1H NMR (200 MHz, DMSO+CDCl3) δ 5.75 (s, 1H), 7.30 (m, 5H), 7.66 (d, 2H, J = 8.30Hz), 8.46 (d, 2H, J = 8.30Hz); EIMS:  m/z 280.&#x0D; 3r: 1H NMR (200 MHz, DMSO+CDCl3): δ 5.5 (s, 1H), 7.26 (d, 2H, J = 8.25Hz), 7.36 (d, 2H, J = 8.25Hz), 7.68 (d, 2H, J = 8.20Hz), 8.49 (d, 2H, J = 8.20Hz); EIMS:  m/z 314.&#x0D; 3s: 1H NMR (200 MHz, DMSO+CDCl3): δ 2.50 (s, 3H), 6.05 (s, 1H), 7.55 (d, 2H, J = 8.26Hz), 7.76 (d, 2H, J = 8.55Hz), 7.80 (d, 2H, J = 8.26Hz), 8.49 (d, 2H, J = 8.55Hz); EIMS:  m/z 294.&#x0D; 3t: IR (KBr): 3425, 1694, 1615, 1500, 1485, 1425, 1179, 616 cm-1; 1H NMR (200 MHz, DMSO+CDCl3): δ 5.75 (s, 1H), 6.46 (s, 1H), 6.65 (s, 1H), 7.4 (s, 1H), 7.66 (d, 2H, J = 8.30Hz), 8.46 (d, 2H, J = 8.30Hz); EIMS:  m/z 270; Anal. Calcd. for C13H10N4O3: C, 57.77; H, 5.119; N, 20.74; O, 17.77. Found: C, 57.78; H, 3.73; N, 20.73; O, 17.76.&#x0D;  &#x0D; References:&#x0D; &#x0D; Almansa, L. A. Gomez, F. L Cavalcanti, A. F. de Arriba, J. Garcia-Rafanell, J. Form, J. Med. Chem., 1997, 40, 547.&#x0D; Daidone, B. Maggio, S. Plescia, D. Raffa, C. Musiu, C. Milia, G. Perra, M. E. Marongiu, Eur. J. Med. Chem., 1998, 33, 375; J. Finn, K. Mattia, M. Morytko, S. Ram, Y. Yang, X. Wu, E. Mak, P. Gallant, D. Keith, Bioorg. Med. Chem. Lett., 2003, 13, 2231.&#x0D; D. Penning, J. J. Talley, S. R. Bertenshaw, J. S. Carter, P. R. Collins, S. Docter, M. J. Graneto, L. F. Lee, J. W. Malecha, J. M. Miyashiro, R. S. Rogers, D. S. Rogier, S. S. Yu, G. G. Anderson, E. G. Burton, J. N. Cogburn, S. A. Gregory, C. M. Koboldt, W. E. Perkins, K. Seibert, A. W. Veenhuizen, Y. Y. Zhang, P. C. Isakson, J. Med. Chem., 1997, 40, 1347; S. Zhihua, J. Guan, F. P. Michael, M. Kathy, W. P. Michael, M. V. William, S. Monica, S. Michele, R. M. Dave, C. Dennis, Bioorg. Med. Chem. Lett., 2000, 10, 601.&#x0D; A. Elvin, E. C. John, C. G. Leon, J. L. John, E. R. Harry, J. Med. Chem., 1964, 7, 259.&#x0D; Pevarello, M. G. Brasca, P. Orsini, G. Traquandi, A. Longo, M. Nesi, F. Orzi, C. Piutti, P. Sansonna, M. Varassi, A. Cameron, A. Vulpetti, F. Roletto, R. Alzani, M. Ciomei, C. Alanese, W. Pastori, A. Marsiglio, E. Pesenti, F. Fiorentini, R. Bischoff, C. Mercurio, J. Med. Chem., 2005, 48, 2944.&#x0D; Fancelli, D. Berta, S. Bindi, A. Cameron, P. Cappella, P. Carpinelli, C. Catana, B. Forte, P. Giordano, M. L. Giorgini, S. Mantegani, A. Marsiglio, M. Meroni, J. Moll, V. Pittala, F. Roletto, D. Severino, C. Soncini, P. Storici, R. Tonani, M. Varasi, A. Vulpetti, P. Vianello, J. Med. Chem., 2005, 48, 3080.&#x0D; Dymek, B. S. Janik, Z. Ryznerski. Acta. Polon. Pharma., 1966, 23, 207.&#x0D; G. Allah, M. M. Hefny, S. A. Salih, M. S. El-Basouny, Corrosion 1989, 45, 574; A. G. Allah, M. W. Badawy, H. H. Reham, M. M. Abou-Romia, J. Appn. Electro Chem., 1989, 19, 928; W. A. Badawy, M. M. Hefny, S. S. El-Egany, Corrosion, 1990, 46, 978; M. M. Abou-Romia, H. A. Abd El-Rahaman, H. A. M. El-Sayed, Bull. Electrochem., 1990, 6, 757.&#x0D; Jagath Reddy, D. Latha, K. Srinivasa Rao, Org. Prep. Proced., 2004, 36, 494; K. C. Joshi, V. N. Pathak, U. Garg, J. Het. Chem., 1979, 16, 1141.&#x0D; Hanefeld, C. W. Rees, A. J. P. White, J. Chem. Soc., Perkin Trance-I, 1996, 1545&#x0D; Vanotti, F. Fiorentini, M. Villa, J. Het. Chem., 1994, 31, 737.&#x0D; S. Dodd, R. L. Martinez, M. Kamau, Z. Ruam, K. V. Kirk, C. B. Cooper, M. A. Hermsmeier, S. C. Traeger, M. A. Poss, J. Comb. Chem., 2005, 7, 584. .&#x0D; R. Khospour, M. M. Kodhoaei, H. Monghannian, Synlett, 2005, 955; A. R. Khospour, K. Esmaeilpoor, A. Moradie, J. Iran. Chem. Soc., 2006, 3, 81; G. Shanmugam, M. Madhavi, P. Anil Kumar, M. Prabhakahr, N. Venu, S. Venkataraman, T. M. Vijayavitthal, G. Mahesh Reddy, Y. Ravindra Kumar, Chemlform, 2005, 36, 46.&#x0D; Larhed, A. Halberg, J. Org. Chem., 1996, 51, 9582; A. Lupy, Topics in Current Chem., 1999, 206, 153; D. Villemin, B. Labiad, A. Loupy, Synth. Commun., 1993, 23, 419; C. D. Wang, S. Xin-Zhong, R. J. Xie, Synth. Commun., 1997, 27, 2517;&#x0D; B. Dorsch, S. M. Mcelvain. J. Amer. Chem. Soc. 1932, 54, 2960; G. Wang, X. Liu, G. Zhao. Tetrahedron: Asymmetry 2005, 16, 1873.&#x0D; &#x0D;  &#x0D;  </jats:p

Will Catalysts Save Our Environment?

Introduction&#x0D; If you own a car, then at some point in your life, you’ll end up having to go to the mechanic to address any emergent car troubles. You may experience engine troubles, slower acceleration, or smoke coming out of your car’s exhaust, only to find out that you have a “bad cat.” What do these cute little furballs have to do with cars?&#x0D; Well, it’s not an actual cat, just in case you were worrying about that. The “cat” in question is a catalytic converter – a component in your car’s exhaust system that contains catalysts to reduce pollution in the environment.&#x0D; Catalysts are materials that speed up chemical reactions by facilitating them such that bond breaking and formation processes require less energy to undergo. During their interaction in the reaction, they do not get spent but rather get recycled as long as the reaction continues.&#x0D; Since the ’70s, catalytic converters have been helping reduce NOX, SOX, COX, and other exhaust waste gases in vehicles and industrial processes throughout the world. This use of catalysts on a major scale ushered in an era of green chemistry where scientists and researchers look for ways to tackle the environmental problems that plague our world. So, will catalysts save our environment?&#x0D; Electrocatalysis&#x0D; These days, scientists are actively working on finding solutions to reducing the carbon dioxide in our environment via carbon capture and utilization technology. This technology works to reduce carbon dioxide into a substance that does not contribute to global warming. The main chemical reaction involves reducing carbon dioxide to carbon monoxide, which can then be&#x0D;  &#x0D; Used to make new compounds that serve as raw materials and fuel for our industries..&#x0D; Figure 1.&#x0D; Catalysts to save the environment&#x0D; Electrocatalytic converters seem like a promising option at the moment because heavy metals like gold and copper, when used as catalysts in the electrochemical cells, have shown promising results in generating CO. More importantly, the process itself requires large amounts of input electrical energy to be successful; however, dwindling renewable energy prices can make the process more economical when used as an energy source.&#x0D; There is a catch, though. Electrocatalysis requires heavy metal catalysts that are non-renewable and less abundant. Additionally, they pose a risk to the environment as they have the potential to contaminate sources of water if disposed of improperly. But as researchers look into more suitable meta-materials, the technology may soon become feasible.&#x0D; Photocatalysis&#x0D; Photocatalysis is a process that requires the use of sunlight as a source of energy to facilitate chemical reactions in the presence of a catalyst. This technology has made strides in wastewater treatment, but recently scientists found that using TiO2 as a catalyst in photochemical reactions for the treatment of water used in agriculture. It has the added benefit of being nontoxic while reducing agricultural contaminants like pesticides, which, if left untreated, can destroy food chains and reduce biodiversity within an ecosystem.&#x0D; Though the research is still new, it is yet to be seen if it can be commercialized into a viable form capable of handling copious amounts of irrigation water.</jats:p

Can the Natural Products Industry Combat Climate Change?

Doing your part to help conserve the environment? Here's how promoting the natural products industry can help combat climate change.   1 2 3 4 5 6 </jats:p

Will Catalysts Save Our Environment?

If you own a car, then at some point in your life, you’ll end up having to go to the mechanic to address any emergent car troubles. You may experience engine troubles, slower acceleration, or smoke coming out of your car’s exhaust, only to find out that you have a “bad cat.” What do these cute little furballs have to do with cars?</jats:p

Will Cultivated Meat Take Over The Food Industry?

Ever since the corona virus pandemic began, a significant chunk of the world population has lost its life. But despite the enormous number of deaths the world has seen, its demand for food seems to be on the rise. The global health crisis has deteriorated the economies worldwide, causing people to lose their jobs at an unimaginable rate. With millions of people employed, the food insecurity graph is rapidly climbing.&#x0D; In October 2020, The UN’s Food and Agriculture Organization (FAO) reported that food insecurity impacts more than 2 billion people, citing an increase of 10 million from October 2019. Suffice to say that the demand for food is climbing, and studies suggest that it will continue to grow, forcing the food industry to feed 10 billion mouths by 2050.&#x0D; And with meat being the primary source of protein, and in general, food, relying on industrial animal agriculture for meat products is getting more and more unsustainable. That is why many food manufacturers have developed environmentally sustainable ways to produce meat in a lab without harming the animals. The meat produced in an artificial environment is cultivated, cell-based, slaughter-free, cultured, cell-cultured, or clean meat. And by the looks of the food market, it seems that cultured meat will take over the entire industry in the future.&#x0D; Cultivated Meat: The Science &#x0D; The science behind cultured meat is pretty simple; experts cut out stem cells from an animal under anesthesia. The procured sample is then placed with nutrients, growth factors, salts, and pH buffers and left to proliferate. The resulting product is slaughter-free meat.&#x0D; Although the process of cultivating faux meat is slow, the industry is beginning to flourish at a remarkable rate.&#x0D; Figure 1.&#x0D; Red meat steak with red chilies and black peppers&#x0D; Staggering Stats&#x0D; Forbes has reported that the global cultivated meat market is expected to grow $15.5m by 2021 and$20m by 2027, and nearly 35% of all meat available in the market by 2040 will be cell-based.&#x0D; According to another study conducted by the Institute of the Future in Palo Alto, cultivated meat will be a standard product in supermarkets by 2023. Despite being a relatively recent synthetic product, cultured meat seems to be going mass-market quite early on in its life. It was only four years ago when an American company created quite a buzz producing meat-less, cell-based meatballs.&#x0D; The Beginning of Cell-Based Meat Industry&#x0D; The California-based company Memphis Meats introduced cultured meatballs four years ago as an alternative to real meat. Since then, the company has been working on mega projects to lunch cell-based meaton a much larger level worldwide. Memphis Meats’ CEO, Uma Valeti, is hell-bent on providing the world with slaughter-free meat to reduce the risk of heart disease and offer an affordable meat-like meat alternative. His corporation is currently working on a pilot plant to produce beef, chicken, and duck on a mass scale.&#x0D; Memphis Meat is not the only player in the market; many other cell-based meat manufacturing companies are also working to scale their businesses to boost supply. San-Francisco’s Artemys Foods, Berkely-based Mission Barns, and San Diego-based BlueNalu are all working on sustainable ways to supply cultivated meat, which includes fish and duck, to the growing world population.</jats:p

Isolation, charectirisation chemical and bilogical properties of polybrominated diphenyl ethers from the sponge Dysidea herbacea

Isolation, charectirisation of polybrominated diphenyl ethers from the sponge Dysidea herbacea is described. The sponge Dysidea herbacea was collected from the Mandapam Coast, Tamilnadu, India. Isolated gram quantities of hydroxylated polybrominated diphenyl ether (HO-PBDE) and semi-synthesized a series of new PBDEs derivatives and tested them for antibacterial and cytotoxic activities.</jats:p

Can Organic Compounds Help Build Better Capacitors?

Want to know about the latest innovation in capacitor technology? Here's how researchers are building better capacitors with organic compounds.&#x0D; Introduction&#x0D; Capacitors are one of the most fundamental passive components in electrical circuits.1 Like batteries, they store a charge, but unlike batteries, they do not discharge at a fairly constant rate. Instead, it depends on the change in voltage between their terminals and the inherent capacitive properties they possess.2-3 Since the voltage between the terminals of a capacitor cannot change instantaneously, they can be used in applications where it needs to be stabilized, governed, and tuned.&#x0D; Capacitors haven't seen much innovation over the years; however, newer high-voltage electrical applications in smart grids, electric vehicles, and signal processing have called for scientists and researchers to design better capacitors that can prevent bottlenecks in future technologies.4-5 Organic compounds may soon change that. But how?&#x0D; Why Problems Plague Capacitors?&#x0D; Before we elaborate on how organic compounds can help us, we need to discuss the problems facing capacitors. Capacitors have two plates of conducting materials separated by an insulating layer. Charged gets stored on the plates by virtue of an electric field when a difference in voltage is applied between the two plates.&#x0D; The insulating layer (dielectric) in the middle facilitates the electric field by preventing an electrical connection between the two plates, determining the capacitance of the component and the energy it stores. Common dielectric materials used in capacitors include paper, metal oxides, and plastics.&#x0D; The problem lies in material selection for the dielectric. These materials tend to break down, degrade, and leak out depending on the voltage, frequency, temperature, and environment of the capacitor. This impacts their longevity and makes them a common point of failure in many electrical and electronic applications. In some cases, their failure may lead to short circuits that impact other components of the electrical circuit.&#x0D; Figure 1.&#x0D; An image of a printed circuit board with different electronic components&#x0D; How Can Organic Compounds Address These Problems?&#x0D; Organic compounds are a class of materials that deal with carbon and its bond with other atoms. Carbon forms strong covalent bonds with other atoms to form compounds that require a strong electric field to strip away electrons; however, at the molecular level, weaker interactive bonds allow the electric current to pass, making organic compounds, as a whole, a weak dielectric material for capacitors.&#x0D; The answer lies in hydrogels and their interaction via supramolecular assembly chemistry. In a paper published in the American Chemical Society in 2018, researchers claimed to have fabricated a solid-state capacitor with plates and dielectric made out of organic compounds PEDOT (poly(3,4-ethylenedioxythiophene)) and PVA poly-vinyl alcohol.&#x0D; The resultant hydrogel electrode and electrolyte enables the flexible capacitor to withstand higher voltages, store more energy, and make it more durable. Although, in its infancy, more researchers are now following the same principle and trying different organic compound configurations that result in better hydrogel combinations.&#x0D; References&#x0D; &#x0D; Hua-Zhong, Yu.; Sylvie, Morin.; Danial, D. M. W.; Philippe, A.; Catherine, H. de V. J. Phys. Chem. B 2000, 104(47), 11157–11161.&#x0D; Knotts, G.; Bhaumik, A.; Ghosh, K.; Guha1, S. Appl. Phys. Lett. 2014, 104, 233301.&#x0D; Marco, S.; Alessandra, V.; Nicolò, R.; Alain, F.; Marco, P.; Paolo, Ariano. Polymer 2015, 56, 131-134.&#x0D; Marco, S.; Mariangela, L.; Andrea, G.; Galder, K.; Inaki, M.; Fabrizio, Pirri, L.; Montanaro, M. Mater. Eng. 2013, 298, 634-643.&#x0D; Pengxian, H.; Gaojie, X.; Xiaoqi, H.; Jingwen, Z.; Xinhong, Z.; Guanglei, Cui. Adv. Ener. Mater. 2018, 8, 1801243.&#x0D; </jats:p

Synthesis of β-keto-sulfones using alkyl/aryl sulphinates in ionic liquids [bmim-BF4] as an efficient and reusable reaction medium

Synthesis of b-keto-sulfones using alkyl/aryl sulphinates in ionic liquids as en efficient and reusable medium is described. Reaction of α-haloketones with sodium alkyl/aryl sulphinates in ionic liquid afforded the corresponding sulfones in excellent yields. Obtained products were characterized using IR, 1HNMR, 13CNMR and Mass Spectroscopy.&#x0D; Introduction&#x0D; b-keto-sulfones are of great importance in organic synthesis. The presence of sulfone group, in an organic compound adds variety to its chemical architecture1 and also enhances the biological activity of the compound. The methylene and methyl sulfones are very good a-carbanion-stabilizing substituents because strong –IE by the sulfone, but they do not involves conjugation with α-protons. However, the presence of keto group at 3rd position to the sulfone group, adds variety to its functionalities, known as b-keto-sulfones, which are very important group of intermediates as they are used in Michael and Knoevenagel reactions,­2,3 in the preparation of acetylenes, allenes, chalcones,4-9 vinylsulfones10 and polyfunctionalized 4H-pyrans.11 In addition, they are useful for the synthesis of optically active b-hydroxysulfones13 and α-halo methylsulfones.14 This has led to development of novel synthetic methodologies for these compounds. Although several methods of synthesis of ketosulfones have been reported in literature, which includes alkylation of metallic arene sulphinates with either α-haloketone15 or α-tosyloxy ketones,16 acylation of alkyl sulfones,17 reactions of diazo sulfones with aldehydes catalyzed by SnCl2,18 reaction of an acid ester with α-sulfonyl carbanions,19 reaction of an acid anhydride with α-sulfonyl carbanions, addition of aldehydes to α-sulfonyl carbanions followed by oxidation of the resulting b-hydroxysulfones,20 oxidation of b-ketosulphides,21 oxidation of b-ketosulfoxides.22 The direct and straightforward method is the treatment of metallic arene sulphinates with α-haloketone.15 However, the low solubility of metal sulphinate salts in organic solvents is the inadequacy.&#x0D; In recent years, the use of ionic liquids (ILs) as green solvents in organic synthetic processes has gained considerable importance due to their solvating ability, negligible vapor pressure, easy recyclability and reusability.23 Recently, we have reported the direct synthesis of α-iodo b-ketosulfones and their base-induced cleavage to afford α-iodo methyl sulfones.24 In continuation of our work, although not novel, we envisaged the synthesis of ketosulfones using sodium alkyl/aryl sulphinates in bmim-BF4 as a ionic liquid, as efficient and reusable reaction medium&#x0D; Scheme 1.&#x0D; In this report (Scheme 1) we describe an efficient method for the synthesis of sulfones using sodium alkyl/aryl sulphinate in bmim-BF4. This method does not need expensive reagents or special care to exclude the moisture from the reaction medium. We chose bmim-BF4, which are inexpensive and readily available for the preparation of ionic liquid. The resulting salt bmim-BF4 being a liquid at room temperature bmim-BF4. We first examined the reaction of phenacyl bromide 1 with sodium p-toluenesulphinate 2 in bmim-BF4 at room temperature to yield the corresponding sulfone 3 in 98 % yield (Table 2, Entry 1). This result were encouraged us to carry out the reaction in ionic liquids. In order to optimize the reaction conditions, we carried out the reaction in different solvents (Table 1). The poor yields in hydroxylic solvents and less polar solvents are probably due to the lower solubility of the sulphinate salt in these solvents, coupled with the fact that the nucleophile (p-MeC6H4SO2-) is solvated in hydroxylic solvents thereby reducing its effective nucleophilicity. It was observed that bmim-BF4 ability to act as a phase transfer catalyst for this transformation and the reaction was complete very fast (Scheme 2). Reaction of different α-haloketones with alkyl/aryl sulphinates proceeded efficiently and smoothly and the products were obtained in good to excellent yields. Various sulfones have been synthesized in facile manner using ionic liquids as an efficient reaction medium (Scheme 1, Table 2). From the forgoing results, it is evident that the bmim-BF4 is an efficient reaction medium for the synthesis of sulfones. Further, it is noticed that the ionic liquid can be recovered and reused for next run without loss of its activity.&#x0D; The formation of the product ketosulfones rather than ketosulphinate ester can be explained by soft hard acid base (SHAB) terminology and it follows a reductive dehalogenation followed by neucliophilic attack of sulphinate sulphur in a concerted manner (Scheme 2).&#x0D; In conclusion we have described synthesis of ketosulfones using sodium sulphinates in bmim-BF4 as an ionic liquid, as efficient and reusable reaction medium. The present procedure for the synthesis of b-ketosulfones has the advantage of high efficient reaction medium with high yields of products and simple work-up procedure, which makes it, is a useful and important addition to the present existing methods.&#x0D; Table 1: Solvent effect on the reaction of phenacyl bromide with sodium p-toluenesulphinate at room temperature&#x0D; Typical experimental procedure: A mixture of α-haloketone (10 mmol) and sodium alky/aryl sulphinate (11 mmol) in bmim-BF4 (5 mL). The reaction was stirred at RT for an appropriate time (Table 1). After completion of the reaction, as monitored by TLC, the product was extracted into diethyl ether (3 x 20 mL). The combined organic extract was evaporated under reduced pressure to give crude product, which was purified by silica column chromatography. The ionic liquid was recovered and for next run without loss of its activity.&#x0D; Acknowledgements&#x0D; The authors are thankful to Director IICT for his constant encouragement and CSIR New Delhi for providing the fellowship.&#x0D; References:&#x0D; &#x0D; (a) Durst, T. Comprehensive Organic Chemistry, Edited by D. H. R. Barton and W. D. Ollis, Peragmon Press: Oxford, UK, 1979. (b) Trost, B. M. Comprehensive Organic Chemistry, Peragmon Press: Oxford, 1991. (c) Simpkins, N. S.; Sulfones in organic synthesis; Edited by Baldwin, J. E. Peragmon Press: Oxford, 1993.&#x0D; Macro, J. L.; Fernandez, I.; Khira, N.; Fernandez, P.; Romero, A. J. Org. Chem. 1995, 60, 6678.&#x0D; Reddy, M. V. R.; Reddy, S. Acta Chim. Hung. 1984, 115, 269.&#x0D; Ihara, M.; Suzuki, S.; Taniguchi, T.; Tokunaga, Y.; Fukumoto, K. Tetrahedron 1995, 51, 9873.&#x0D; Baldwin, J. E.; Adlington, R. M.; Crouch, N. P.; Hill, R. L.; Laffeg, T. G. Tetrahedron Lett. 1995, 36, 7925.&#x0D; Reddy, M. V. R.; Reddy, S. Acta Chim. Hung. 1985, 120, 275.&#x0D; Looker, J. J. J. Org. Chem. 1966, 31, 2714.&#x0D; Sengupta, S.; Sarma, D. S.; Mondal, S. Tetrahedron 1998, 54, 9791.&#x0D; Sengupta, S.; Sarma, D. S.; Mondal, S. Tetrahedron: Asymmetry 2001, 12, 513.&#x0D; Sengupta, S.; Sarma, D. S.; Mondal, S. Tetrahedron: Asymmetry 1998, 9, 2311.&#x0D; (a) Marco, J. L.; Fernandez, I.; Khiar, N.; Fernandez, P.; Romero, A. J. Org. Chem. 1995, 60, 6678. (b) Marco, J. L. J. Org. Chem. 1997, 62, 6575.&#x0D; Corey, E. J.; Chavosky, M. J. Am. Chem. Soc. 1964, 86, 1639. (b) Trost, B. M.; Arndt, H. C.; Strege, P. E.; Verhowever, T. R. Tetrahedron Lett. 1976, 27, 3477. (c) Kurth, M. J.; Brien, M. J. J. Org. Chem. 1985, 50, 3846. (d) Fuju, M.; Nakamura, K.; Mekata, H.; Oka, S.; Ohno, A. Bull. Chem. Soc. Jpn. 1988, 61, 495. (e) Sengupta, S.; Sarma, D. S.; Mondal, S. Tetrahedron 1998, 54, 9791. (f) Guo, H.; Zhang. Y. Synth. Commun. 2005, 30, 2564.&#x0D; (a) Svatos, A.; Hun Kova, Z.; Kren, V.; Hoskovec, M.; Saman, D.; Valterova, I.; Vrkoc, J.; Koutek, B. Tetrahedron: Asymmetry 1996, 7, 1285. (b) Betus, P.; Phansavath, P.; Vidal, V. R.; Genet, J. P.; Touati, A. R.; Homri, T.; Hassine, B. B. Tetrahedron: Asymmetry 1999, 10, 1369. (c) Gotor, V.; Rebolledo, F.; Liz, R. Tetrahedron: Asymmetry 2001, 12, 513. (d) Ni, C.; Li, Y.; Hu, J, J. Org. Chem, 2006, 71, 6829.&#x0D; (a) Baker, F. C.; Li, J. P. N. United States Patent January 27, 1981, US4247559, (C07D 207/452; A61K 031/40). (b) Eckstein, Z.; Zavistowska, M.; Palut, D.; Polubiec, E. Pol. J. Chem. 1966, 45, 314. (c) Ejmocki, Z.; Krassowska, B. K.; Olezak, I.; Eckstein, Z. Pol. J. Chem. 1980, 54, 11 and 2153. (d) Antane, S.; Bernotas, R.; Li, Y.; David. Mc. R.; Yan, Y. Synth. Commun. 2004, 34, 2443.&#x0D; Vennstra, G. E.; Zwaneburg, V. Synthesis 1975, 519.&#x0D; (a) Xie, Y. -Y.; Chen, Z. -C. Synth. Commun. 2001, 31, 3145. (b) Kumar, D.; Sundaree, S.; Rao, V. S.; Rajender, S. V. Tetrahedron Lett. 2006, 47, 4197.&#x0D; (a) Kartizky, A. R.; Abdel-Fattah, A. A.; Wang, M. Y. J. Org. Chem. 2003, 68, 1443. (b) Truce, W. E.; Knospe, R. H. J. Am. Chem. Soc. 1995, 5063.&#x0D; Holmquist, C. R.; Roskamp, E. J. Tetrahedron Lett. 1992, 33, 1131.&#x0D; Schank, K.; Weber, A. Synthesis 1970, 367. (b) Schank, K. Annalen 1967, 75, 702. (c) Grossert, J. S.; Dubey, P. K.; Gill, G. H.; Stancey, T.; Cameron, T. S.; Patric, A. G. Can. J. Chem. 1984, 62, 798.&#x0D; Julia, M.; Paris, J. M. Tetrahedron Lett. 1973, 14, 4833.&#x0D; Durst, T. Comprehensive Organic Chemistry, Edited by D. H. R. Barton and W. D. Ollis, Peragmon Press; Oxford, UK, 1979, 4, Chap.11.8, 174.&#x0D; Trost, B. M. Chem. Rev. 1978, 78, 363.&#x0D; Fukumoto, K.; Yoshizavwa, M.; Ohno, H. J. Am. Chem. Soc. 2005, 127, 2398. (b) Fukumoto, K.; Yoshizavwa, M.; Ohno, H. Chem. Commun. 2006, 3081. (c) Wang, C.; Guo, L.; Li, H.; Wang, Y.; Weng, J.; Wu, L. Green Chem. 2006, 8, 603.&#x0D; (a) Suryakiran, N.; Srikanth Reddy, T.; Asha Latha, K.; Lakshman, M.; Venkateswarlu, Y. Tetrahedron Lett. 2006, 47, 3853. (b) Suryakiran, N.; Srikanth Reddy, T.; Suresh, V.; Lakshman, M.; Venkateswarlu, Y. Tetrahedron Lett. 2006, 47, 4319. c) Suryakiran, N.; Prabhakar, P.; Srikanth Reddy, T.; Chinni Mahesh, K.; Rajesh, K.; Venkateswarlu, Y. Tetrahedron Lett. 2006, 47,&#x0D; Fukumoto, K.; Yoshizavwa, M.; Ohno, H. J. Am. Chem. Soc. 2005, 127, 2398. (b) Fukumoto, K.; Yoshizavwa, M.; Ohno, H. Chem. Commun. 2006, 3081. (c) Wang, C.; Guo, L.; Li, H.; Wang, Y.; Weng, J.; Wu, L. Green Chem. 2006, 8, 603.&#x0D; (a) Suryakiran, N.; Srikanth Reddy, T.; Asha Latha, K.; Lakshman, M.; Venkateswarlu, Y. Tetrahedron Lett. 2006, 47, 3853. (b) Suryakiran, N.; Srikanth Reddy, T.; Suresh, V.; Lakshman, M.; Venkateswarlu, Y. Tetrahedron Lett. 2006, 47, 4319. c) Suryakiran, N.; Prabhakar, P.; Srikanth Reddy, T.; Chinni Mahesh, K.; Rajesh, K.; Venkateswarlu, Y. Tetrahedron Lett. 2006, 47, 8039.&#x0D; </jats:p